Pharmacokinetics and bioequivalence evaluation of two oral formulations of topiramate tablets in healthy Chinese male volunteers under fasting and fed conditions.

Topiramate is an antiepileptic drug (AED) that is effective in treating various types of epilepsy. This study evaluated the bioequivalence and safety of two topiramate tablets in healthy Chinese subjects under fasting and fed conditions. We designed an open-label, randomized, single-dose, two-period, crossover trial protocol.

Reorganization of cortical individualized differential structural covariance network is associated with regional morphometric changes in chronic subcortical stroke.

Patients with chronic subcortical stroke undergo regional and network morphometric reorganizations beyond the lesion site, but the interplay between network and regional reorganization remains poorly understood. We aimed to clarify the reorganization patterns of the individualized differential structural covariance networks (IDSCN) in chronic subcortical stroke and investigate their associations with regional gray matter volume (GMV) changes and functional recovery. Structural MRI from four datasets enrolled 112 patients with chronic subcortical stroke (81 male, age: 55.

Determination of eldecalcitol in human plasma by SIL-IS UPLC-APCI-MS/MS method for pharmacokinetics study.

Eldecalcitol is a novel analog of 1α,25-dihydroxyvitamin D [1,25(OH)D] for the treatment of patients with osteoporosis. A highly sensitive and specific ultra-performance liquid chromatography coupled to atmospheric pressure chemical ionization tandem mass spectrometry (UPLC-APCI-MS/MS) technique featuring a lower limit of quantitation (LLOQ) as low as 5 pg/ml, has been established and validated for the rapid and accurate quantification of eldecalcitol in human plasma samples. Plasma samples were extracted by solid phase extraction (SPE).

A physiologically-based quantitative systems pharmacology model for mechanistic understanding of the response to alogliptin and its application in patients with renal impairment.

Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In this study, we developed a comprehensive physiologically-based quantitative systematic pharmacology model of the alogliptin-glucose control system to predict plasma exposure and use glucose as a clinical endpoint to prospectively understand its therapeutic outcomes with varying renal function. Our model incorporates a PBPK model for alogliptin, DPP-4 activity described by receptor occupancy theory, and the crosstalk and feedback loops for GLP-1-GIP-glucagon, insulin, and glucose.

Bioinformatics-based screening of key genes associated with gemcitabine resistance in advanced pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest cancers globally. Despite gemcitabine being a primary chemotherapeutic agent, many patients with PDAC develop resistance, significantly limiting treatment efficacy. This study aims to screen and validate key genes associated with gemcitabine resistance in advanced PDAC using bioinformatics analysis and clinical sample validation, thereby providing potential noninvasive biomarkers and therapeutic targets for overcoming chemoresistance.

Impact of prolonged surgical waiting time on cancer-specific mortality in stage I-II pancreatic ductal adenocarcinoma patients who received radical resection.

Background: The impact of prolonged surgical waiting time (SWT) on the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains controversial. This study aimed to explore the impact of prolonged SWT on PDAC-specific mortality (PSM).

Methods: The data of patients with stage I-II primary PDAC who received radical resection were obtained from the Surveillance, Epidemiology, and End Results database.

DBU-catalyzed annulation strategy for modular assembly of 2,3-difunctionalized dihydrobenzofurans.

An organocatalytic approach for the construction of 2,3-dihydrobenzofuran scaffold through a formal [4 + 1] annulation of 2-(2-nitrovinyl)phenols and α-bromoacetophenones in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) has been developed.

Intra-arterial tenecteplase after successful endovascular recanalisation in patients with acute posterior circulation arterial occlusion (ATTENTION-IA): multicentre randomised controlled trial.

Objective: To assess whether intra-arterial tenecteplase administered after successful endovascular recanalisation improves outcomes in patients with acute arterial occlusion of the posterior circulation.

Design: Multicentre randomised controlled trial.

Setting: 31 hospitals in China, 24 January 2023 to 24 August 2023.

Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke: The POST-UK Randomized Clinical Trial.

Importance: Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion.

Objective: To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion.

Integrative machine learning frameworks to uncover specific protein signature in neuroendocrine cervical carcinoma.

Objective: Neuroendocrine cervical carcinoma (NECC) is a rare but highly aggressive tumor. The clinical management of NECC follows neuroendocrine neoplasms and cervical cancer in general. However, the diagnosis and prognosis of NECC remain dismal.

FLASH radiotherapy: mechanisms, nanotherapeutic strategy and future development.

Ultra-high dose-rate (FLASH) radiotherapy serves as an ideal procedure to treat tumors efficiently without harming normal tissues and has demonstrated satisfactory antitumor effects in multiple animal tumor models. However, the biological mechanisms of FLASH radiotherapy have not yet been fully elucidated, and the small number of devices delivering FLASH dose rate has limited its wide application. This review summarizes the possible biological mechanisms and antitumor effects of FLASH radiotherapy, its application in nanotherapeutic strategy, as well as its challenges and future development.

Adipose-derived mesenchymal stem cells combined with platelet-rich plasma are superior options for the treatment of osteoarthritis.

Background: There is currently no definitive treatment for osteoarthritis. We examined the therapeutic effects and underlying mechanisms of platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells (ADSCs), individually or in combination, in a rat model of anterior cruciate ligament-induced degenerative osteoarthritis (OA) of the knee. This study seeks to advance clinical approaches to OA treatment.

Prediction of prognosis in patients with cerebral contusions based on machine learning.

Traumatic brain injury (TBI) is a global issue and a major cause of patient mortality, and cerebral contusions (CCs) is a common primary TBI. The haemorrhagic progression of a contusion (HPC) poses a significant risk to patients' lives, and effectively predicting changes in haematoma volume is an urgent clinical challenge that needs to be addressed. As a branch of artificial intelligence, machine learning (ML) can proficiently handle a wide range of complex data and identify connections between data for tasks such as prediction and decision making.

Construction of a multifunctional bio-probe based on lanthanides for UCL/MR/CT multimodal imaging.

Multimodal bioimaging is beneficial for clinical diagnosis and research due to the provision of comprehensive diagnostic information. However, the design of multifunctional bio-probes aggregating multiple bioimaging functions is greatly challenging. In this study, a multifunctional bio-probe based on lanthanide-based nanomaterials SrGdF: Yb/Er/Tm(abbreviated as SGF) was developed formultimodal imaging by co-adopting apropos lanthanides and tuning their molar ratio.

Excess Ub-K48 Induces Neuronal Apoptosis in Alzheimer's Disease.

Background: K48-linked ubiquitin chain (Ub-K48) is a crucial ubiquitin chain implicated in protein degradation within the ubiquitin-proteasome system. However, the precise function and molecular mechanism underlying the role of Ub-K48 in the pathogenesis of Alzheimer's disease (AD) and neuronal cell abnormalities remain unclear. The objective of this study was to examine the function of K48 ubiquitination in the etiology of AD, and its associated mechanism of neuronal apoptosis.

Examining the effects of psychological resilience and wellbeing on perceived stress and depressive symptoms among undergraduate nursing interns: testing a moderated mediation model.

Background: Perceived stress is recognized as a significant risk factor for depressive symptoms, while psychological resilience and wellbeing are considered crucial protective factors. However, the intricate relationships among these variables in undergraduate nursing interns remain largely unexplored. This study aims to investigate the mediating role of psychological resilience in the relationship between perceived stress and depressive symptoms, as well as the moderating influence of wellbeing on this mediation.

Targeting AURKA with multifunctional nanoparticles in CRPC therapy.

Castration-resistant prostate cancer (CRPC) presents significant therapeutic challenges due to its aggressive nature and poor prognosis. Targeting Aurora-A kinase (AURKA) has shown promise in cancer treatment. This study investigates the efficacy of ART-T cell membrane-encapsulated AMS@AD (CM-AMS@AD) nanoparticles (NPs) in a photothermal-chemotherapy-immunotherapy combination for CRPC.

Biomechanical changes in lumbar intervertebral discs after percutaneous endoscopic transforaminal discectomy surgery at different Body Mass Index (BMI) categories.

Objective: Percutaneous Endoscopic Transforaminal Discectomy (PETD) is recognized as the leading surgical intervention for lumbar disc herniation (LDH). Moreover, Body Mass Index (BMI) has been established as an independent risk factor for disc reherniation post-PETD. Furthermore, there is a lack of studies investigating the biomechanical changes in the disc post-PETD in relation to diverse BMI levels.

Systemic Infection Affecting Multiple Sites After Near-Drowning: A Case Report.

() can cause fungal infections in near-drowning victims, and an increasing number of cases have been reported. However, cases of bone and joint infections caused by are rare. In this case, a 35-year-old otherwise healthy Chinese female presented with aspiration pneumonia and knee arthritis after accidentally falling into sewage and near-drowning and underwent macrogenomic second-generation sequencing of arthrocentesis fluid, which showed .

[Characteristics and treatment measures of cages displacement after oblique lateral interbody fusion].

Objective: To explore characteristics, management strategies and preventive measures of fusion device displacement after oblique lateral interbody fusion (OLIF) in treating lumbar lesions.

Methods: The clinical data of 12 patients with fusion device displacement after OLIF for lumbar lesions in 4 medical centers from October 2014 to December 2018 were retrospectively analyzed, including 4 males and 8 females, aged from 53 to 81 years old;2 patients with lumbar disc degeneration, 4 patients with lumbar spinal stenosis, 3 patients with lumbar degenerative spondylolisthesis and 3 patients with lumbar degenerative kyphosis;preoperative dual-energy X-ray bone mineral density (BMD) was detected in 1 patient with T-value > -1 SD, 5 patients with T-value >-1~-2.5 SD, and 6 patients with T-value <-2.

4-Hydroxychalcone attenuates AngII-induced cardiac remodeling and dysfunction via regulating PI3K/AKT pathway.

Cardiac remodeling encompasses structural alterations such as hypertrophy, fibrosis, and dilatation, alongside numerous cellular and molecular functional aberrations, constituting a pivotal process in the advancement of heart failure (HF). 4-Hydroxychalcone (4-HCH) is a class of naturally occurring compounds with variable phenolic structures, and has demonstrated the preventive efficacy in hyperaldosteronism, inflammation and renal injury. However, the role of 4-HCH in the regulation of cardiac remodeling remains uncertain.